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Epigenetic Alteration of HIST1 in Acute Myeloid Leukemia With NPM1 Mutation

By: Kelly M. Hennessey, PhD
Posted: Sunday, March 1, 2020

Patients with acute myeloid leukemia (AML) frequently have mutations in the nucleophosmin 1 (NPM1) gene. Their prognosis depends upon treatment, which is guided by cytogenetics and molecular alterations. A recent study identified a correlation between favorable patient prognosis and epigenetic alteration of H3K27me3 HIST1 in the mutated NPM1 gene, according to Sylvain Garciaz, PhD, of Aix Marseille University, France and colleagues. Their work was published in Clinical Epigenetics.

In gene-expression profiling, the H3K27me3 HIST1high mark was associated with lower expression of the histone genes HIST1H1D, HIST1H2BG, HIST1H2AE, and HIST1H3F. The prognosis for patients with AML and a mutation in the NPM1 gene depends on the epigenetic silencing of the HIST1 cluster. According to the study authors, the importance of the H3K27me3 accumulation at the HIST1 locus may be the downregulation of the histone genes affected by the repressive epigenetic mark. Levels of histone gene expression may indicate the aggressiveness of the disease and potentially may guide therapeutic choices.

The researchers performed chromatin immunoprecipitation–quantitative polymerase chain reaction on patient samples included in two GOELAMS clinical trials (ClinicalTrials.gov identifiers NCT00860639 and NCT00590837) to characterize the H3K27me3 HIST1 mark. They found that H3K27me3 HIST1high patients experienced a median overall survival of 50.9 months compared with 14.6 months for H3K27me3 HIST1low patients. The median event-free survival was 37 months for the H3K27me3 HIST1high group and 9 months for the H3K27me3 HIST1low group. Thus, detection of the epigenetic biomarker in AML demonstrates that H3K27me3 HIST1high status may be associated with a favorable outcome and potentially less-aggressive disease.

“Our study pinpoints the H3K27me3 HIST1 mark and HIST1H1D gene as two biomarkers potentially useful to stratify patient prognosis and defines targets that can be considered when developing epidrugs,” concluded the investigators.

Disclosure: The study authors reported no conflicts of interest.



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